Synthetic resin matrix system for the extended delivery of drugs

• US 4,747,845 A
• Filed: 01/03/1986
• Issued: 05/31/1988
• Est. Priority Date: 10/17/1983
• Status: Expired due to Fees

• Current Assignee: Enquay Pharmaceutical Associates A Partnership Consisting of Bernard Korol and Paul Nathan
• Original Assignee: Enquay Pharmaceutical Associates
• Inventors: Korol, Bernard
• Primary Examiner(s): Phillips, Delbert R.
• Assistant Examiner(s): Nutter, Nathan M.
• Application Number:
  US06/815,874
• Time in Patent Office: 879 Days
• Field of Search: 424/19, 424/26, 424/28, 514/708, 514/709, 514/936, 514/946, 514/965, 524/104, 524/111, 524/167, 524/173, 524/233, 524/296, 524/317, 523/111, 523/122, 604/368, 128/156, 128/334, 128/335.5
• US Class Current: 604/368
• CPC Class Codes: A61L 15/24 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof A61L15/225 takes precedence
• CPC Class Codes: A61L 15/44 Medicaments
• CPC Class Codes: A61L 2300/40 characterised by a specific therapeutic activity or mode of action
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 26/0014 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 26/008 Hydrogels or hydrocolloids
• CPC Class Codes: C08L 33/14 of esters containing halogen, nitrogen, sulfur, or oxygen atoms in addition to the carboxy oxygen

Abstract

A synthetic resin matrix system for the delayed and extended duration delivery of drugs to humans and animals is disclosed consisting of a polymer, such as poly(2-hydroxyethylmethacrylate), referred to as PHEMA, an organic solvent, such as polyethylene glycol (PEG), and a hydrogen binding plasticizer, such as dimethylsulfoxide (DMSO). The plasticizer regulates the set-up time of the synthetic resin so that the more plasticizer present, the shorter the set-up time. The plasticizer also has a direct shortening effect upon the cure time and also profoundly influences many of the physical characteristics of the resultant synthetic resin matrix system. A variety of drugs can be embodied in the fabricated matrix system and administered to the patient (or animal) by different modes of application, including but not limited to oral, topical, rectal, subcutaneous implant, or organ-specific implant such as in the conjunctival sac of the eye. These formulations and procedures can also be utilized in the storage and extended-duration delivery of agricultural products, particularly herbicides, insecticides, and nutritional supplements. By manipulating the relative concentrations of the components of the matrix system and the particle size of the embedded active agent, it is possible to control the release dynamics of the active embodied agent from the matrix and thus provide unique controlled delayed and extended delivery of the active agent.

Claims

1. A synthetic resin matrix system for drug storage and extended duration drug release comprising a particulate, hydrophilic, water swellable polymer, an inert, non-toxic water miscible organic solvent, and a hydrogen bonding plasticizer, said polymer selected from the group consisting of hydroxy(C₂ -C₄ -alkyl) methacrylate, hydroxy(C₂ -C₄ alkyl) acrylate, hydroxy(C₂ -C₄ alkoxyC₂ -C₄ alkyl) methacrylate, hydroxy(C₂ -C₄ alkoxyC₂ -C₄ alkyl) acrylate, alkoxy(C₂ -C₄ alkoxyC₂ -C₄ alkyl) methacrylate, alkoxy(C₂ -C₄ alkoxyC₂ -C₄ alkyl) acrylate, N-(C₁ -C₄ alkyl) acrylamide, N-(C₁ -C₄ alkyl) methacrylamide, N,N-di(C₁ -C₄ alkyl) acrylamide, N,N-di(C₁ -C₄ alkyl) methacrylamide, vicinal-epoxy(C₁ -C₄ alkyl) methacrylate, or vicinal-epoxy(C₁ -C₄ alkyl) acrylate, said solvent selected from the group consisting of polyethylene glycol or polypropolene glycol having a molecular weight averaging between about 200-2000 gram molecules weight units, and wherein said plasticizer being selected from the group consisting of dimethylsulfoxide, dimethylphthalate, 2,3-butylene carbonate, dimethylformamide, dimethyltetramethylene sulfone, diethylsulfone, methylene glycolate, methylpropyl sulfone, or butyrolactone, with said polymer ranging between about 15%-50% by weight of said matrix system, with said solvent ranging between about 30%-65% by weight of said matrix system, and with said plasticizer ranging up to about 20% by weight of said matrix system.

2. A synthetic resin matrix system for drug storage and extended duration drug release as set forth in claim 1, wherein the preformed configuration of the matrix system allows for the administration of the matrix system to ailing animals or humans by different modes of application including one of oral, rectal, topical, sublingual, subcutaneous implant, and organ-specific placement.

3. A synthetic resin matrix system for drug storage and extended duration drug release as set forth in claim 1, further comprising a medicament agent for local or systemic therapeutic effects, said medicament agent from pharmacological classes of drugs such as antimicrobial, antibiotic, analgesic, anticovulsant, antipsychotic, hormone, antihistamine, cardiovascular, anxiolytic, antispasmodic, skeletal muscle relaxant, antiviral, antineoplastic, diuretic, antiparasitic, healing enhancer, respiratory, and learning and memory enhancers.

4. A synthetic resin matrix system for chemical storage and extended duration release as set forth in claim 1, wherein the prefabricated configuration of the matrix system allows for the administration of the matrix containing agriculture products, particularly herbicides, insecticides, or nutritional supplements.

5. A synthetic resin matrix system for drug or chemical storage as set forth in claim 1, wherein the release rate of the embodied drug or chemical is controlled by the particle size, and its surface area, or the embodied active agent in a manner such that large embodied particles having small surface area are released at a slower rate than smaller particles with relatively larger surface area.

6. The invention of claim 3 and wherein said included drugs comprising of silver sulfadiazine, nitrofurazone, hydrocortisone, hydrocortisone acetate, and hydrocortisone sodium succinate, nitroglycerine, diltiazem hydrochloride, urapidil fumerate, urapidil, and cimetidine.

7. The invention of claim 6 and wherein said drug synthetic resin matrix system being encapsulated.